Author Correction: Increased lactate dehydrogenase activity is dispensable in squamous carcinoma cells of origin.

The original version of this Article contained an error in the spelling of the authors J. H. Joly and N. A. Graham, which were incorrectly given as J. Jolly and N. Graham. Additionally, the affiliation of both authors with 'Mork Family Department of Chemical Engineering and Materials Science, University of Southern California, Los Angeles, CA 90089' and N. A. Graham with 'Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90089' was inadvertently omitted. This has now been corrected in both the PDF and HTML versions of the Article.

Increased lactate dehydrogenase activity is dispensable in squamous carcinoma cells of origin.

Although numerous therapeutic strategies have attempted to target aerobic glycolysis to inhibit tumor progression, these approaches have not resulted in effective clinical outcomes. Murine squamous cell carcinoma (SCC) can be initiated by hair follicle stem cells (HFSCs). HFSCs utilize aerobic glycolysis, and the activity of lactate dehydrogenase (Ldh) is essential for HFSC activation. We sought to determine whether Ldh activity in SCC is critical for tumorigenesis or simply a marker of the cell type of origin. Genetic abrogation or induction of Ldh activity in HFSC-mediated tumorigenesis shows no effect on tumorigenesis as measured by number, time to formation, proliferation, volume, epithelial to mesenchymal transition, gene expression, or immune response. Ldha-null tumors show dramatically reduced levels of glycolytic metabolites by metabolomics, and significantly reduced glucose uptake by FDG-PET live animal imaging. These results suggest that squamous cancer cells of origin do not require increased glycolytic activity to generate cancers.

Olfactory mucosal lesions following subcutaneous diethyldithiocarbamate (DDTC).

We found that a single 600 mg/kg subcutaneous dose of the chelating agent diethyldithiocarbamate (DDTC) in rats caused severe damage of the olfactory epithelium. Damage was characterized by degeneration of the receptor cells but sparing of basal cells. This degeneration was characterized centrally (in the olfactory bulb) by 50% shrinkage of glomeruli. Reactive gliosis, as judged by immunoreactivity for glial fibrillary acidic protein, was prominent in the glomeruli at one week. Glomeruli areas had recovered to control values and gliosis in glomeruli had decreased by five weeks after injection. This recovery corresponds to sparing of the regenerative cell of the olfactory epithelium. We hypothesized that DDTC may act by disrupting xenobiotic metabolic pathways requiring divalent cations.

Bilateral functioning uterine anlagen with the Rokitansky-Mayer-Kuster-Hauser syndrome.

This report describes an adolescent female with a shallow vaginal pouch and bilateral functioning uterine anlagen, who presented with cyclic pelvic pain and a pelvic mass. Removal of both functioning uterine anlagen afforded complete relief of symptoms.

Effects of perphenazine and bromocriptine on male accessory sex glands. III. The prostate gland.

The in vivo morphologic effects of androgen, perphenazine (a prolactin release stimulator), and bromocriptine (a prolactin release inhibitor) on the ventral prostate glands of immature intact and castrate C3H/HeJ mice were studied. Normal prostatic stromal and epithelial development was controlled by testicular androgens. Stromal proliferation and epithelial degeneration followed prepubertal castration at 21 d of age. These changes were reversed after 17-19 or 35-37 d of testosterone administration for 2 wk. In castrate mice, perphenazine administration produced near normal epithelial morphology, whereas bromocriptine stimulated principal cell hyperplasia with basal cell enlargement and increased mitotic activity. In the absence of testicular androgens, prolactin may partially control epithelial proliferation.

Effects of bromocriptine and perphenazine on male accessory sex glands II. Ultrastructure of the seminal vesicles.

The effects of prolactin (PRL) and androgen on the seminal vesicles of immature C3H/HeJ mice were studied. Glands from controls exhibited secretory activity and full differentiation. Glands from castrates were small, markedly atrophic with some stromal hyperplasia and moderate leukocytic infiltration. Testosterone-treated castrates were similar to intact controls. Perphenazine appeared to stimulate the rough endoplasmic reticulum (RER), Golgi, and secretory activity of the epithelium in the intact and castrated mice. Normal secretory granules were not made in the perphenazine-treated castrates, but a flocculent material usually was present in the RER, Golgi, and secretory vacuoles. Bromocriptine reduced cell height and secretory activity in intact mice and promoted anaplasia and epithelial proliferation in castrates. PRL seems to be required for the seminal vesicles to complete and maintain cytological development, but the effect of PRL may be different in the presence or absence of testicular androgens.

Effects of anionic xenobiotics on rat kidney. I--Tissue and mitochondrial respiration.

The polar 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT) metabolite, 2,2-bis(p-chlorophenyl)acetic acid (DDA), and the phenoxyacetic acid herbicides, 2,4-dichlorophenoxyacetic acid (2,4-D) and 2,4,5-trichlorophenoxyacetic acid (2,4,5-T), were previously shown to be accumulated to high levels in liver and kidney via the organic acid transport system, raising the possibility of organ-specific toxicity secondary to transport. In these studies, accumulation of DDA was shown to depress oxygen consumption by renal cortical slices at high doses (0.1 and 1mM). Isolated renal and hepatic mitochondria were uncoupled by low doses of DDA (5-10 nmoles/mg mitochondrial protein. Maximal uncoupling was seen at 50-70 nmoles/mg. 2,4-D and 2,4,5-T also produced uncoupling, but at doses of 70 nmoles/mg or higher. All agents were more effective with alpha-ketoglutarate or pyruvate-malate), all three agents also depressed State 3 (ADP-stimulated) respiration. Again, DDA was more effective than 2,4-D or 2,4,5-T. These results suggest that accumulation of these or other anionic xenobiotics may lead to toxicity in those tissues possessing the organic anion transport system.

Amiloride-sensitive ammonium and sodium ion transport in the blue crab.

In the estuarine crab, Callinectes sapidus, net NH4+ efflux was twice as high in animals acclimated to 17% salinity seawater (SW) (0.495 +/- 0.084 mumol . h-1 . g wet wt-1, n = 7) than in animals acclimated to full-strength 35% SW (0.212 +/- 0.028 mumol . h-1 . g-1, n = 7). Amiloride (3 X 10(-4) M) in the external SW reversibly inhibited these effluxes by 63 +/- 6% (n = 6) and 67 +/- 6% (n = 5), respectively. Unidirectional Na+ influx was reversibly inhibited 42 +/- 6% (n = 7) by amiloride in 17% SW-acclimated crabs and 49 +/- 7% (n = 8) in 35% SW-acclimated crabs. This mutual sensitivity to amiloride is evidence for a Na+/NH4+ exchanger. Inhibition of unidirectional Na+ efflux by Na+-free SW indicates the presence of an obligate Na+/Na+ exchange component that accounts for at least 42% of the Na+ flux and is also amiloride sensitive. The lack of inhibition by amiloride of the net H+ efflux does not support the presence of a Na+/H+ exchanger. Acclimation of the crab to dilute SW may involve an increase in the activity of the Na+/NH4+ exchanger in the gills, but this mechanism contributes only a small fraction of the total Na+ transport.

Effects of bromocriptine and perphenazine on male accessory sex glands. I. The seminal vesicles.

The effects of bromocriptine and perphenazine on C3H/HeJ mouse seminal vesicles were studied. The response of the stroma and parenchyma of the glands to the hormones differed. Testosterone repressed stromal proliferation. Prolactin had no observable stromal effect but influenced the response of the parenchyma. In castrated mice, low levels of prolactin were associated with abnormal epithelial mitotic activity and atypical cytology while elevated prolactin levels resulted in a nonatrophic epithelium similar to that from the seminal vesicles of intact individuals. In the absence of testicular testosterone, prolactin may exert an inhibitory influence on glandular proliferation.